PMID- 21381023
OWN - NLM
STAT- MEDLINE
DCOM- 20111208
LR  - 20240320
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 227
IP  - 1
DP  - 2012 Jan
TI  - Mechanisms of ATP release by human trabecular meshwork cells, the enabling step 
      in purinergic regulation of aqueous humor outflow.
PG  - 172-82
LID - 10.1002/jcp.22715 [doi]
AB  - Our guiding hypothesis is that ecto-enzymatic conversion of extracellular ATP to 
      adenosine activates A(1) adenosine receptors, reducing resistance to aqueous 
      humor outflow and intraocular pressure. The initial step in this purinergic 
      regulation is ATP release from outflow-pathway cells by mechanisms unknown. We 
      measured similar ATP release from human explant-derived primary trabecular 
      meshwork (TM) cells (HTM) and a human TM cell line (TM5). Responses to 21 
      inhibitors indicated that pannexin-1 (PX1) and connexin (Cx) hemichannels and 
      P2X(7) receptors (P2RX(7) ) were comparably important in modulating ATP release 
      induced by hypotonic swelling, whereas vesicular release was insignificant. 
      Consistent with prior studies of PX1 activity in certain other cells, ATP release 
      was lowered by the reducing agent dithiothreitol. Overexpressing PX1 in HEK293T 
      cells promoted, while partial knockdown (KD) in both HEK293T and TM5 cells 
      inhibited hypotonicity-activated ATP release. Additionally, KD reduced the 
      pharmacologically defined contribution of PX1 and enhanced those of Cx and 
      P2RX(7) . ATP release was also triggered by raising intracellular Ca(2+) activity 
      with ionomycin after a prolonged lag time and was unaffected by the PX1 blocker 
      probenecid, but nearly abolished by P2RX(7) antagonists. We conclude that 
      swelling-stimulated ATP release from human TM cells is physiologically mediated 
      by PX1 and Cx hemichannels and P2X(7) receptors, but not by vesicular release. 
      PX1 appears not to be stimulated by intracellular Ca(2+) in TM cells, but can be 
      modulated by oxidation-reduction state. The P2RX(7) -dependent component of 
      swelling-activated release may be mediated by PX1 hemichannels or reflect 
      apoptotic magnification of ATP release, either through itself and/or 
      hemichannels.
CI  - Copyright (c) 2011 Wiley Periodicals, Inc.
FAU - Li, Ang
AU  - Li A
AD  - Department of Physiology, School of Medicine, University of Pennsylvania, 
      Philadelphia, Pennsylvania 19104-6085, USA.
FAU - Leung, Chi Ting
AU  - Leung CT
FAU - Peterson-Yantorno, Kim
AU  - Peterson-Yantorno K
FAU - Stamer, W Daniel
AU  - Stamer WD
FAU - Mitchell, Claire H
AU  - Mitchell CH
FAU - Civan, Mortimer M
AU  - Civan MM
LA  - eng
GR  - R01 EY013624/EY/NEI NIH HHS/United States
GR  - EY01583/EY/NEI NIH HHS/United States
GR  - R01 EY013624-09/EY/NEI NIH HHS/United States
GR  - EY17007/EY/NEI NIH HHS/United States
GR  - EY15537/EY/NEI NIH HHS/United States
GR  - P30 EY001583/EY/NEI NIH HHS/United States
GR  - R01 EY017007/EY/NEI NIH HHS/United States
GR  - R01 EY015537/EY/NEI NIH HHS/United States
GR  - EY13624/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Connexins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (PANX1 protein, human)
RN  - 0 (Receptors, Purinergic P2X7)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - K72T3FS567 (Adenosine)
SB  - IM
MH  - Adenosine/metabolism
MH  - Adenosine Triphosphate/*metabolism
MH  - Aqueous Humor/*metabolism
MH  - Blotting, Western
MH  - Connexins/metabolism
MH  - Glaucoma/metabolism/physiopathology
MH  - HEK293 Cells
MH  - Humans
MH  - Intraocular Pressure/*physiology
MH  - Luminescent Measurements
MH  - Microscopy, Confocal
MH  - Nerve Tissue Proteins/metabolism
MH  - Real-Time Polymerase Chain Reaction
MH  - Receptors, Purinergic P2X7/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Trabecular Meshwork/cytology/*metabolism
PMC - PMC3117029
MID - NIHMS277871
EDAT- 2011/03/08 06:00
MHDA- 2011/12/13 00:00
PMCR- 2013/01/01
CRDT- 2011/03/08 06:00
PHST- 2011/03/08 06:00 [entrez]
PHST- 2011/03/08 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
PHST- 2013/01/01 00:00 [pmc-release]
AID - 10.1002/jcp.22715 [doi]
PST - ppublish
SO  - J Cell Physiol. 2012 Jan;227(1):172-82. doi: 10.1002/jcp.22715.